Worst Pills, Best Pills

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Drug Profile

The information on this site is intended to supplement and enhance, not replace, the advice of a physician who is familiar with your medical history. Decisions about your health should always be made ONLY after detailed conversation with your doctor.

Limited Use [what does this mean?]
Generic drug name: esomeprazole (e so MEP ra zole)
Brand name(s): NEXIUM, NEXIUM 24HR
GENERIC: available FAMILY: Proton Pump Inhibitors
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: lansoprazole (lan SOP ra zole)
Brand name(s): PREVACID, PREVACID 24HR
GENERIC: available FAMILY: Proton Pump Inhibitors
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: omeprazole (o MEP ra zole)
Brand name(s): PRILOSEC, PRILOSEC OTC, YOSPRALA
GENERIC: available FAMILY: Proton Pump Inhibitors
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: pantoprazole (pan TOE pra zole)
Brand name(s): PROTONIX
GENERIC: available FAMILY: Proton Pump Inhibitors
Find the drug label by searching at DailyMed.

Limited Use [what does this mean?]
Generic drug name: rabeprazole (ra BE pray zole)
Brand name(s): ACIPHEX
GENERIC: available FAMILY: Proton Pump Inhibitors
Find the drug label by searching at DailyMed.

Pregnancy and Breast-feeding Warnings [top]

Pregnancy Warning

Omeprazole caused harm to developing fetuses in animal studies, including deaths of embryos and disruptions of pregnancies. Use these drugs during pregnancy only for clear medical reasons. Tell your doctor if you are pregnant or thinking of becoming pregnant before you take these drugs.

Breast-Feeding Warning

These drugs are excreted in the milk of rats and reach levels higher than in the mother's blood. Because of the ability of these drugs to cause DNA damage and tumors in rats and mice, you should not take these drugs while nursing.

Safety Warnings For This Drug [top]

Nighttime Heartburn Treatments: Try These First

There are nondrug treatments, with no safety concerns, and less expensive drugs that may be effective for you; these should be tried before you use any drugs for heartburn. First, try to avoid foods that trigger your condition (e.g., fatty foods, onions, caffeine, peppermint, and chocolate), and avoid alcohol, smoking, and tight clothing.[1] Second, avoid food, and particularly alcohol, within two or three hours of bedtime. Third, elevate the head of the bed about six inches or sleep with extra pillows.

For both heartburn and ulcers, it is important to avoid drug-induced causes. Aspirin, ibuprofen, and other nonsteroidal anti-inflammatory drugs (NSAIDs) are known to cause ulcers. Ask your doctor if acetaminophen could be substituted for these drugs. Check with your doctor about the osteoporosis medications alendronate (FOSAMAX) and risedronate (ACTONEL), which irritate the esophagus.

If these measures are not effective, try simple over-the-counter (OTC) antacids such as a generic aluminum hydroxide and magnesium hydroxide product (MAALOX, MAALOX TC). If symptoms worsen or bleeding occurs, call your doctor. If this does not relieve your symptoms, one of the family of stomach acid–blocking drugs known as histamine2-blockers can be tried. This family includes cimetidine (TAGAMET), famotidine (PEPCID), nizatidine (AXID), and ranitidine (ZANTAC). Histamine2-blockers are available in both OTC and prescription strengths.

If the OTC histamine2-blockers do not give adequate relief of your symptoms after 14 days, it is time to consult your physician.

In long-term (two-year) studies in rats, all the drugs in this class caused an increase in carcinoid tumors of the stomach. Although such tumors have not yet been demonstrated in humans, using these drugs for long-term therapy is not advisable, except for the treatment of Zollinger-Ellison syndrome.

Facts About This Drug [top]

Esomeprazole (NEXIUM), lansoprazole (PREVACID), omeprazole (PRILOSEC), pantoprazole (PROTONIX) and rabeprazole (ACIPHEX) are close chemical relatives in a family of ulcer drugs known as proton pump inhibitors (PPIs). Public Citizen lists them all as Limited Use drugs (offer limited benefits or benefit certain people or conditions).

These drugs are approved for short-term treatment of gastroesophageal reflux disease (GERD), and all of them but pantoprazole also are approved for duodenal and...

Esomeprazole (NEXIUM), lansoprazole (PREVACID), omeprazole (PRILOSEC), pantoprazole (PROTONIX) and rabeprazole (ACIPHEX) are close chemical relatives in a family of ulcer drugs known as proton pump inhibitors (PPIs). Public Citizen lists them all as Limited Use drugs (offer limited benefits or benefit certain people or conditions).

These drugs are approved for short-term treatment of gastroesophageal reflux disease (GERD), and all of them but pantoprazole also are approved for duodenal and stomach ulcers that are resistant to treatment with antacids and histamine2-blockers. In addition, all PPIs except pantoprazole are approved for use in combination with antibiotics to treat ulcer disease caused by the bacterium Helicobacter pylori (H. pylori; see "Combination Treatments for Helicobacter Pylori Infection").

All five drugs are indicated for the treatment of Zollinger-Ellison syndrome, a rare hormonal disorder in which a stomach tumor causes excessive stomach acid production. The PPIs do not alter the course of this syndrome.

PPIs completely inhibit the secretion of stomach acid, whereas histamine2-blockers, such as cimetidine (TAGAMET), partially prevent production of the acid. Histamine2-blockers relieve heartburn pain more quickly than do PPIs.[2]

Treatment of ulcers takes up to six weeks; for Zollinger-Ellison syndrome, treatment time is indefinite. To maintain effectiveness in treating Zollinger-Ellison syndrome, the dose may need to be increased annually.[3] Patients who do not have H. pylori infection and who have increased acid secretion after discontinuing a PPI may require long-term use of these drugs.[4]

Doctors frequently overprescribe PPIs; for many people, these drugs are prescribed unnecessarily, putting patients at unnecessary risk of adverse effects. See our Worst Pills, Best Pills News articles from March 2008 and November 2011 for more information concerning the overuse of PPIs.

Patients who have been taking omeprazole since it was approved in 1989 have actually been getting esomeprazole with each dose. Like many drugs, omeprazole is a mixture of two forms that are chemically identical mirror images of each other. These mirror images are called optical isomers, and esomeprazole is one of the two that make up omeprazole. Esomeprazole and omeprazole are both produced by the same company: AstraZeneca Pharmaceuticals.

Use in children

The drug product label for omeprazole states that in patients younger than one year, the safety and effectiveness of omeprazole in the treatment of GERD or other pediatric uses have not been established.[5]

The use of PPIs to treat acid reflux symptoms in infants is at an all-time high. These drugs present serious safety risks to adults and young children, and the staggering increase in PPI use comes despite the fact that until 2011, no drug from this class had been approved by the Food and Drug Administration (FDA) for use in children younger than 1 year.

In 2011, the FDA's approval of esomeprazole, another PPI, for the treatment of erosive esophagitis in children from one month to one year of age represented the first — and so far only — approval of a PPI for any indication in children younger than one year. The approval was based not on a clinical study conducted in infants for this indication, but rather on questionably inferring safety and effectiveness from studies in adults and children older than one year. The only randomized trial evaluating esomeprazole's effectiveness in infants showed the drug to be no more effective than a placebo. To this day, no PPI has been shown to be effective for GERD in infants.[6]

Rabeprazole also is approved for the short-term treatment of symptomatic GERD in patients 12 years of age and older and for short-term treatment of GERD in children one to 11 years of age.[7]

Adverse effects

Relapse of acid reflux is common.

Long-term acid suppression may lead to intestinal infections.[8] It is uncertain whether long-term suppression of stomach acid also may cause stomach cancer.[9],[10] After long-term treatment, vitamin B12 stores may be depleted in strict vegetarians and the elderly; vitamin B12 levels should be monitored in these patients.[8],[11]

A type of kidney inflammation called interstitial nephritis has been associated with omeprazole since 2000. This condition also has been reported with pantoprazole and lansoprazole.[12] Two studies published in 2016 suggest that PPI use may be associated with chronic kidney disease.[13],[14] Both studies showed that the risk of harm to the kidneys increased when PPIs were used at higher doses or for longer periods of time.

Published studies have suggested that there may be an increased risk of fractures in people taking PPIs, and the FDA has changed the product labels of these drugs to reflect this risk.

Low serum magnesium levels may occur if use of a PPI lasts longer than one year. Symptoms of low magnesium levels may include muscle spasm, irregular heartbeat and convulsions.

PPIs also are linked to Clostridium difficile-associated bacterial diarrhea, which can be fatal in some patients.

Lupus erythematosus is an autoimmune disease that causes the body's immune system to attack healthy tissue. Cutaneous (affecting the skin) and systemic (affecting multiple organs, which may include the skin, joints, kidneys, lungs, heart and nervous system) lupus erythematosus have been reported with use of PPIs.[15]

Long-term use of PPIs may lead to stomach polyps, which only rarely develop into cancer.

Interactions with other drugs

A study published in 2008 investigating the effect of omeprazole on the action of clopidogrel (PLAVIX) plus aspirin therapy found that omeprazole significantly decreased the effect of the antiplatelet drug clopidogrel. This means that clopidogrel could be less effective in preventing strokes and heart attacks when used with omeprazole. Physicians and patients should be aware of this association because this drug combination is widely prescribed.[16]

A 2009 study in the Canadian Medical Association Journal found that people taking clopidogrel for a recent heart attack in combination with lansoprazole, omeprazole or rabeprazole — but not pantoprazole — had a 40% higher risk of having another heart attack compared with people who used only clopidogrel. This increased risk was probably caused by the PPI drugs blocking activation of clopidogrel.

Also, the FDA has stated that using cilostazol (a drug used to improve the flow of blood, listed on WorstPills.org as Do Not Use and available only in generic form) with omeprazole or esomeprazole is expected to increase the levels of cilostazol in the body.

Studies show...

Most studies do not show significant differences among the various PPIs for the treatment of GERD or duodenal ulcer.[17]

In April 2016, JAMA Neurology published a study showing that regular PPI use was associated with an increased risk of new dementia.[18]

Regulatory actions surrounding PPIs

2004: The "Warnings and Precautions" section of the pantoprazole product label was revised to include a drug interaction with warfarin (COUMADIN, JANTOVEN), a blood-thinning agent, which may lead to an increased risk of bleeding in patients taking the two drugs together.[19]

2007: The FDA added interstitial nephritis to the lansoprazole product label.[20]

The FDA also issued a communication concerning new safety data for omeprazole and esomeprazole. The results from two small, long-term clinical studies raised concerns that long-term use of these drugs may increase the risk of heart attack, heart failure and heart-related sudden death in those patients taking either of the drugs, compared with patients who had surgery to control their GERD. The FDA stated that health care providers should not change their prescribing practices and patients should not change their use of these products.[21]

In December, the FDA issued follow-up communications stating that the available data did not suggest an increased risk of heart problems for patients treated with these drugs.[22]

2009: The FDA issued a public advisory stating that it was aware of some reports that suggested that PPIs may make clopidogrel less effective in some patients. The makers of clopidogrel worked with the FDA to obtain additional information in relation to these reports.[23]

The FDA changed the clopidogrel drug label to warn that using certain classes of drugs that inhibit the activity of clopidogrel (such as omeprazole in the PPI family) should be discouraged in patients taking clopidogrel.[24]

In November, the FDA updated the product label of clopidogrel to state that administration of omeprazole and clopidogrel within 12 hours of each other reduces the effectiveness of clopidogrel. The warning also stated that this reduction in the effectiveness of clopidogrel was not observed with other drugs used to reduce stomach acid, except for cimetidine or antacids.[25]

2010: The FDA issued safety-labeling changes concerning the use of cilostazol and esomeprazole or omeprazole. The updated information stated that using cilostazol with esomeprazole or omeprazole was expected to increase the levels of cilostazol in the body.[26]

The FDA also issued safety-labeling changes indicating that the use of PPIs can cause an increased risk of osteoporosis-related fractures of the hip, wrist or spine. This advisory was based on published studies suggesting that there may be an increased risk of fractures in people taking these medications. The FDA stated that the increased risk of fractures was noted in patients who were using PPIs for a year or longer and who were taking multiple daily doses.[27]

2011: In March, the FDA updated PPI product labels to warn of low serum magnesium levels when PPIs are taken for a long period of time — usually longer than one year.[28]

In May, another FDA advisory stated that low serum magnesium levels had been reported rarely in patients treated with PPIs for at least three months, but in most cases, the condition was reported after a year of therapy. Most of these patients were treated for hypomagnesemia with magnesium replacement and discontinuation of the PPI. The FDA also stated that patients who are on prolonged treatment with PPIs or who take PPIs with medications such as digoxin (LANOXIN) or drugs that may cause hypomagnesemia (for example, diuretics) may need to have their magnesium levels monitored prior to initiation of PPI treatment and periodically thereafter.[28]

In August, Public Citizen petitioned the FDA to immediately add black-box warnings and other safety information concerning several severe risks to the product labels of all PPIs on the market in the U.S. (esomeprazole, dexlansoprazole [DEXILANT], omeprazole, omeprazole and sodium bicarbonate [ZEGERID], lansoprazole, pantoprazole, rabeprazole, esomeprazole and naproxen [VIMOVO]; PRILOSEC OTC, ZEGERID OTC, PREVACID 24-HR; and all other generic counterparts).

We petitioned the FDA to require black-box warnings on the labels of PPIs identifying the following risks related to use of these drugs: rebound acid hypersecretion, which results in dependence on these frequently overused drugs; fracture; C. difficile-associated diarrhea; and magnesium deficiency. We also petitioned the FDA to update the labels for all PPIs to include a description of interactions with clopidogrel, methotrexate (OTREXUP, RASUVO, TREXALL; a drug used for treating rheumatoid arthritis, certain cancers and other conditions) and mycophenolate mofetil (CELLCEPT; a drug used in organ transplantation); the risks of vitamin B12 deficiency and acute interstitial nephritis; and recommendations on length of treatment when used for GERD.

In addition, the petition stated that the serious nature of so many of these adverse reactions mandates the creation of an FDA-approved patient Medication Guide.

On Oct. 31, 2014, the FDA granted some of the actions requested in our petition and denied others. Specifically, the FDA agreed with and granted the following requests:

  • In the labeling of all PPI products, the addition of information regarding the risk of C. difficile-associated diarrhea and the risk of drug-drug interactions between PPIs and mycophenolate mofetil (anti-transplant rejection drug) and methotrexate (for rheumatoid arthritis and other conditions);
  • In the labeling of certain PPI products (omeprazole and esomeprazole), the addition of information regarding the risk of drug-drug interactions with clopidogrel;
  • In the labeling of certain prescription PPI products, the addition of information regarding the risks of vitamin B12 deficiency and acute interstitial nephritis and certain information regarding treatment length for GERD; and
  • The issuance of Medication Guides for certain prescription PPI products regarding certain safety risks.

2012: In February, the FDA issued an advisory that PPIs may be associated with an increased risk of C. difficile-associated diarrhea. Patients who take a PPI and develop diarrhea that does not improve should be evaluated for a C. difficile infection.[29] The FDA required PPI manufacturers to include information about this risk in the drugs' labels.

2013: In April, Health Canada (the Canadian equivalent to the FDA) also issued a warning regarding the risk of fractures associated with the use of PPIs. This warning was similar to the FDA's 2010 safety-labeling changes.[30]

2018: The FDA approved updates to the drug product labels of PPIs to warn that long-term use of PPIs is associated with an increased risk of stomach polyps.[31]

Before You Use This Drug [top]

Tell your doctor if you have or have had:

  •   allergies to drugs in this class
  •   heart problems[32]
  •   Helicobacter pylori infection
  •   liver problems
  •   pernicious anemia[32],[33]
  •   pregnancy or are breast-feeding

Tell your doctor about any other drugs you take, including aspirin, herbs, vitamins, and other nonprescription products.

When You Use This Drug [top]

  • Call your doctor immediately if you have black, tarry stools or if you vomit material that looks like coffee grounds. These are signs of a bleeding ulcer.
  • Call your doctor if you have trouble swallowing or persistent abdominal pain.
  • Check with your doctor if your symptoms do not improve or get worse.
  • Do not drink alcohol or smoke.
  • Avoid any food or drink that aggravates your ulcer.
  • Check with your doctor before taking any aspirin, ibuprofen, or other NSAIDs. These drugs can cause or aggravate ulcers.

How to Use This Drug [top]

  • If you miss a dose, take it as soon as you remember, but skip it if it is almost time for the next dose. Do not take double doses.
  • Do not share your medication with others.
  • Take the drug at the same time(s) each day.
  • Swallow capsule whole. Do not crush, chew, or open the capsule.
  • Take the tablet in the morning, with or without food (pantoprazole).
  • Take the capsule form immediately before a meal, preferably breakfast (omeprazole, lansoprazole).
  • If you cannot swallow the capsule whole, capsules may be opened and the contents mixed with apple juice (and swallowed immediately) or mixed with applesauce, jelly, or ketchup, then swallowed without chewing or crushing.
  • Take antacids for pain relief for several days until pain relief begins or until your doctor tells you.
  • Take the full course of therapy.
  • Store at room temperature with lid on tightly. Do not store in the bathroom. Do not expose to heat, moisture, or strong light. Keep out of reach of children.

Interactions with Other Drugs [top]

The following drugs, biologics (e.g., vaccines, therapeutic antibodies), or foods are listed in Evaluations of Drug Interactions 2003 as causing “highly clinically significant” or “clinically significant” interactions when used together with any of the drugs in this section. In some sections with multiple drugs, the interaction may have been reported for one but not all drugs in this section, but we include the interaction because the drugs in this section are similar to one another. We have also included potentially serious interactions listed in the drug’s FDA-approved professional package insert or in published medical journal articles. There may be other drugs, especially those in the families of drugs listed below, that also will react with this drug to cause severe adverse effects. Make sure to tell your doctor and pharmacist the drugs you are taking and tell them if you are taking any of these interacting drugs:

ADALAT, ADALAT CC, BIAXIN, bismuth subsalicylate, carbamazepine, caffeine, CARAFATE, cilostazol, clarithromycin, COUMADIN, cyclosporine, DIASTAT, diazepam, DILANTIN, ELIXOPHYLLIN, ketoconazole, methotrexate, moclobemide, nifedipine, NEORAL, NIZORAL, NORVIR, PEPTO-BISMOL, phenytoin, PLETAL PREVPAC, PROCARDIA, PROCARDIA XL, ritonavir, SANDIMMUNE, SLO-BID, sucralfate, TEGRETOL, THEO-24, theophylline, TREXALL, VALIUM, warfarin.

Adverse Effects [top]

Call your doctor immediately if you experience:

  •   abdominal or stomach pain
  •   anxiety
  •   appetite increased or decreased
  •   bleeding or bruising that is unusual
  •   bloody urine
  •   breathing interruptions
  •   chest pain
  •   chest tightness or wheezing
  •   chills, fever, or sore throat
  •   constipation
  •   convulsions or seizures (rabeprazole)
  •   cough
  •   depression
  •   diarrhea
  •   eye or eyelid puffiness or swelling
  •   hive-like swellings on eyelids, face, lips, mouth, and/or tongue
  •   muscle or joint pain
  •   nausea or vomiting
  •   rectal bleeding
  •   shortness of breath
  •   skin color changes in the face
  •   skin peeling or redness
  •   skin rash or itching
  •   thirst that is unusual
  •   tiredness or weakness that is unusual
  •   ulcers or sores on mouth that are persistent
  •   urination painful
  •   urine frequency or volume increased
  •   yellow eyes or skin

Call your doctor if these symptoms continue:

  •   abdominal pain
  •   anxiety
  •   chills
  •   confusion
  •   constipation
  •   cough
  •   diarrhea
  •   dizziness
  •   drowsiness or tiredness that is unusual
  •   ears buzzing or ringing
  •   gas
  •   headache
  •   heartburn
  •   hoarseness
  •   joint or back pain
  •   moving difficulty
  •   muscle rigidity
  •   nausea or vomiting
  •   numbness, tingling, pain, or weakness in hands or feet
  •   skin itchy
  •   sleeping difficulty
  •   throat sore
  •   vision blurred
  •   weakness

Signs of overdose:

  •   abdominal pain
  •   confusion
  •   drowsiness
  •   flushing
  •   headache
  •   heartbeat fast or irregular
  •   ill feeling
  •   mouth dry
  •   nausea or vomiting
  •   vision blurred

If you suspect an overdose, call this number to contact your poison control center: (800) 222-1222.

last reviewed March 31, 2021